Review
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Cardiol. May 26, 2014; 6(5): 314-326
Published online May 26, 2014. doi: 10.4330/wjc.v6.i5.314
Autoantibodies to apolipoprotein A-1 as a biomarker of cardiovascular autoimmunity
Nicolas Vuilleumier, Fabrizio Montecucco, Oliver Hartley
Nicolas Vuilleumier, Fabrizio Montecucco, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 1211 Geneva, Switzerland
Nicolas Vuilleumier, Fabrizio Montecucco, Department of Human Protein Sciences, Faculty of Medicine, 1211 Geneva, Switzerland
Fabrizio Montecucco, Department of Internal Medicine, Foundation for Medical Researches, Faculty of Medicine, Geneva 1211, Switzerland
Oliver Hartley, Department of Immunology and Pathology, Faculty of Medicine, 1211 Geneva, Switzerland
Author contributions: All the authors contributed to this manuscript.
Supported by Swiss National Science Foundation Grants to Dr. Vuilleumier N No. 310030_140736; and to Dr. Montecucco F No. 32003B_134963/1; a grant from the Foundation “Gustave and Simone Prévot” to Dr. Montecucco F
Correspondence to: Dr. Nicolas Vuilleumier, MD, PD, Head of Laboratory Medicine Division, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva, Switzerland. nicolas.vuilleumier@hcuge.ch
Telephone: +41-22-3729150   Fax: +41-22-3827245
Received: December 23, 2013
Revised: February 5, 2014
Accepted: March 17, 2014
Published online: May 26, 2014
Processing time: 178 Days and 19.6 Hours
Abstract

Immune-driven inflammation plays an important part in atherogenesis and is therefore believed to be key to the development of cardiovascular disease (CVD), which is currently the leading cause of death in the Western world. By fulfilling some of the Koch postulates, atherogenesis has even been proposed to be considered as an autoimmune disease, raising the hope that CVD could be prevented by immunomodulation. Nevertheless, the role of the immune system and autoimmune reactions in atherosclerosis appear to be a double edged-sword, with both pro-atherogenic and anti-atherogenic attributes. Hence, if immunomodulation is to become a therapeutic option for atherosclerosis and CVD, it will be crucial to correctly identify patients who might benefit from targeted suppression of deleterious autoimmune responses. This could be achieved, for example, by the detection of disease-associated autoantibodies. In this work, we will review the currently available clinical, in vitro, and animal studies dedicated to autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG), the major proteic fraction of high density lipoprotein. Current clinical studies indicate that high levels of anti-apoA-1 IgG are associated with a worse cardiovascular prognosis. In addition, in vitro and animal studies indicate a pro-inflammatory and pro-atherogenic role, supporting the hypothesis that these autoantibodies may play a direct causal role in CVD, and furthermore that they could potentially represent a therapeutic target for CVD in the future.

Keywords: Autoantibodies; Cardiovascular disease; Atherosclerosis; Apolipoprotein A-1; Autoimmunity; Biomarkers

Core tip: This review provides a comprehensive and critical analysis of the most recent basic research articles and clinical trials on the role of autoantibodies to apolipoprotein A-1 as biomarkers and potential mediators of cardiovascular diseases (CVD). Evidence from both in vitro and in vivo studies showed that anti-apolipoprotein A-1 IgG might have critical pro-atherosclerotic activities by activating immune cells to release pro-inflammatory mediators and proteases. In addition, these autoantibodies might increase heart rate and arrhythmias both in humans and animal models. These studies suggest a causal role of anti-apolipoprotein A-1 immunoglobulins of G class in CVD, indicating that those autoantibodies could potentially represent an emerging therapeutic target to better fight CVD.